The heart is a vital organ, being responsible for pumping oxygenated and nutrient rich blood to the body. Efficient functioning of the heart can be compromised by trauma, infection and ischaemia. Ischaemic heart disease is the leading cause of death in industrialised countries, often manifesting clinically as a myocardial infarction (MI). The management of ischaemic heart disease essentially relies upon one of three strategies, including medical therapy, percutaneous coronary intervention (PCI) and coronary artery bypass grafting. Although medical treatment remains the mainstay of anti-ischaemic therapy, many patients undergo additional, invasive therapy in an attempt to restore coronary blood flow.
While there has been some success in preventing second and subsequent myocardial infarctions, acute MI strikes the majority of sufferers without prior warning. It is generally not possible to predict (and therefore prevent) a primary infarction, with the inevitable result being that a certain amount of irreparable damage to cardiac tissue occurs.
Mammalian heart has been considered terminally differentiated with a static number of cardiomyocytes that are incapable of self-renewal. There is emerging evidence that limited number of replicating cardiomyocytes and stem cells are participating in the process of cellular maintenance and myocardial regeneration in patients with heart failure. Beltrami, A. P., Urbanek, K., Kajstura, J., Yan, S. M., Finato, N., Bussani, R. et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med. 2001; 344:1750-7. Urbanek, K., Quaini, F., Tasca, G., Torella, D., Castaldo, C., Nadal-Ginard, B. et al. Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci USA. 2003; 100:10440-5. However, the numbers of cells involved in this process are believed to have insignificant effect in the repair of major injuries such as myocardial infarction. There is therefore a clear need in the art for methods to repair damaged myocardium after an ischaemic event or that due to other causes of myocardial damage.
It is an aspect of the present invention to at least alleviate a problem of the prior art by providing specific cells directed towards a lineage suitable for repair of the myocardium.